The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with Idiopathic Pulmonary Fibrosis

DSpace/Manakin Repository

The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with Idiopathic Pulmonary Fibrosis

Citable link to this page

. . . . . .

Title: The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with Idiopathic Pulmonary Fibrosis
Author: Xue, Jianmin; Gochuico, Bernadette R.; Alawad, Ahmad Samer; Feghali-Bostwick, Carol A.; Noth, Imre; Nathan, Steven D.; Dacic, Sanja; Ocak, Iclal; Fuhrman, Carl R.; Cuenco, Karen T.; Jacobs, Susan S.; Zeevi, Adriana; Morel, Penelope A.; Pilewski, Joseph M.; Valentine, Vincent G.; Gibson, Kevin F.; Kaminski, Naftali; Sciurba, Frank C.; Zhang, Yingze; Rosen, Glenn David; Rosas, Ivan O.; Smith, Mary A.; Duncan, Steven R.

Note: Order does not necessarily reflect citation order of authors.

Citation: Xue, Jianmin, Bernadette R. Gochuico, Ahmad Samer Alawad, Carol A. Feghali-Bostwick, Imre Noth, Steven D. Nathan, Glenn D. Rosen, et al. 2011. The HLA class II allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis. PLoS ONE 6(2): e14715.
Full Text & Related Files:
Abstract: Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients. Methods/Principal Findings: HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3–2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DLCO) compared to the 184 disease subjects who lacked this allele (37.861.7% vs. 42.861.4%, p = 0.036). Conclusions/Significance: DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease.
Published Version: doi:10.1371/journal.pone.0014715
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044131/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:8461943

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters